Certain i-tert-amino lower alkyl



United States Patent Ofiice 3,004,978 CERTAZN L'I'ERT-AMHJO LOWER ALKYL AZABENZEMIBAZOLES Alfred Hunger, Jindrich Kehrle, and Alberto RQSSlyBESfil, and Karl Holfmann, Binningen, Switzerland, assignors to Ciba Pharmaceutical Products Inc., Summit, NJ. No Drawing. Filed Mar. 15, 1960, Ser. No. 15,057 Claims priority, application Switzerland Mar. 18, 1959 7 Claims. (Cl.260294.8)

This invention provides l-low'er'tertiary ar'niiio lbw'er alkyl-azabenzimidazol'es, especially l-lower trtiary ar'nino-lower alkyl-7-aza-benzimidazole's, and "acid I addition salts of these compounds. The compounds may be substiin which A represents a lower alkylene radical, having 1-5 carbon atoms, and R represents a lower tertiary amino group, for example an alkylene-imiho group, which may be interrupted by a heteroatom, such as a piperidino, pyrrolidino, piperazino or morpholino group, but especially a di-lower aLkylamino group, and in which R represents a hydrogen or halogen atom-r a 'hydroxy, mercapto, alkyl, alkoxy, alkylmercapto group, and

C H: ([JH: N t ht) 1 represents a pyridine ring substituted by a nitro group, and especially 1-(B-diethylaminoethyl)-5-nitro-7-azaben= zimidazole, and salts of these compounds.

The new azabenzimidazoles are obtainable by methods in themselves known. One process consists, ,tor example, in forming the a'zabenzimidazol'e ring by ring closure in which amino-lo'w'er'alkyl-amino)-3-amino=pyridine may be 'iib- 3,004,978 Patented 17 1961 'startingfrom 'an amino pyridine, which contains in ortho- .position to the amino fgroupa lowertertiary an'lino'lowr alkylarniho group or a s'ubstituent convertible intosuch group, for example, a hydroxyalkylamino group, or a corresponding N-substituted derivative thereof. Tli'e substituent convertible into-a lower tertiary "amino lower alkylamino group is then converted into such "group, in the case of a hydroxy-"alkyl amino group, for example, by chlorination followed by reaction with a lower sec-- ondary amine. Thus, for example, a '2-(lowerjtertiafy 'jected directly or insfages to ring fclosure with analkariic acid, for example, formic acid, acetic acid or propionic acid, or a re'aCtiVe functional-derivative of such acid, es-

pecially an ester "thereof 'with an alcohol fth'at splitsoff easily or imin'o-ether thereof, or with a carb'onicbrt'hiocarbonic acid derivative. The final products can "also be made by using 'for the'condensation, instead'of alkanic acid, an alkane-aldehyd'e or a functional derivative there} of, and oxidising the product so obtained.

In the aforesaid reactions the starting materials may he formed under the reaction conditions. Thus, forex- -ample, it is of advantage to subject for example, an

acylamino-pyridine, which contains *a halogen atomin -ortho-position to the amino group, to ring closure with a lower tertiary amino lower alkylamine to form the corresponding 'azabenzimidazole derivative.

Another process for making the new compounds consis'ts in introducing into the l-positionof an aizab'enzi'ini- 'dalzole directly or in stages a lower tertiary amino lower alkyl group. Thus, an aza'be'nzimida' zole may be reac't'ed with a reactiv'e'ester -o'f an alcohol of the formula HO A -R' in which A has the meaning given above, and R 'repre- 'sents a lower tertiary amino group or a'substitue'n't convertible into'such group, 'for example, a hydroxyl group, -and,'when the resulting compound contains a substituent convertible into a lower tertiary amino group, the said subst-ituent is so converted, for example, a hydroxyl group by chlorination followed by reaction with a lower secondary amine. Reactive esters 'are more especially those of strong inorganic or organic acids, such as hydrohalic acids or inorganic sulfonic acids such as para-toluene sulfonic acid. The introduction is advantageously carried out in the presence of a condensing agent, especially one capable of forming a 'inetal'salt with the azabenzimidazole, such as an alkali metal or alkaline earth metal, Tor-Example, sodium, lithium or calcium, or ah amide, hydride, hydrocarbon compound, 'alcoholate, pxide or hydroiiide of such metal, for example, sodai'nide, sodium hydride, lithium butyl, potassium henyl, lithium phenyl, potassium tertiary 'butylate, potassium tertiary -amylate,-sodiiim ethylate, sodium oxide or sodium hydroxide, or with the use of the preformed metal salt of the benziiiiidazole. When th'e'reaction leads to a mixture of position isomers, the mixture is separated into its components, for exam, ple, by crystallization of the bases or salts thereof.

Substituents maybe introduced into the ir'nidazole o'r pyridine nucleus 'of the products, or existing substituiit's may be replaced by other 'substituents, for example, a hydroxyl group may be converted into an etherified or esterified hydroxyl group, such as a lower alkoxy group, or a nitro group may be converted into an amino group and the latter into a lower alkox'y group or a halogen atom.

The reactions are-carried out inthepre'seacebr absence of a diluent and/or condensing agent, when 'nces's'ary, at a raised temperature under atmospheric or superatmospheric pressure. V

Depending on the procedure used the new compounds are obtained in the form of the tree bases or salts thereadministration.

'of. From the salts the free bases can be obtained by methods in themselves known. From the free bases salts canrbe made by reaction with acids suitable for making therapeutically useful salts, for example, hydrohalic acid, sulfuric acid, nitric acid, phosphoric acid, thiocyanic acid, acetic acid, propionic acid, oxalic acid, malonic acid, .suc'cinic acid, maleic acid, methane sulfonic acid, ethane sulfonic acid, oxyethane sulfonic acid, benzene or toluene sulfonic acid or a therapeutically active acid.

The starting materials are known or can be made by methods in themselves known. The invention also includes any modification of the process in which there is used as starting material a compound obtainable as an intermediate product at any stage of the process and the remaining steps of the process are carried out. a i The new compounds can be used as medicaments, for example, in the form of pharmaceutical preparations Qwhich containthe compound or a salt thereof in admixture with a pharmaceutical organic or inorganic, solid or liquid carrier suitable for enteral, parenteral or topical For making the carriers there are used substances that do not react with the new compound, for example, water, gelatine, lactose, starches, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums, polyalkylene glyccls, White petroleum jelly, cholesterol or other known carrier for medicants. The pharmaceutical preparations may be in the form, for example, of tablets, .dragees, salves, creams or in liquid form as solutions, suspensions or emulsions If desired they may be sterilized and/or may contain auxiliary substances, such as preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure or buffers. They may. also contain other therapeutically useful substances. The following examples illustrate the invention:

Example 1 6 grams of 2-(e-diethylamino-ethylamino)-3-arnino-5- nitropyridine, dissolved in 10 ml. of formic acid, are boiled under reflux for one hour, after which the excess of formic acid is removed in vacuo, the residue is dissolved in water, the base is liberated by means of ammonia, and is filtered off after cooling. The resulting l-(fi-diethylamino-ethyl)-5-nitro-7-azabenzimidazole of the formula in 50 ml. of toluene, while stirring, and the whole is then boiled under reflux for 2 hours. 50 ml. of a 2 N-solution of caustic soda are stirred into the cooled reaction mixture, the toluene layer is separated in a separating funnel, the base is extracted with 2 N-hydrochloric acid; and then liberated from the aqueous solution by means of ammonia. The base is taken up in ether, the ethereal solution is dried with magnesium sulfate, the solvent is removed. and the residue is distilled under a high vacuum. Z-(B-diethylamino-ethylamino) -3 :S-dinitro-pyridine of the formula 4 is a yellow crystalline substance which melts at 66 C. Its hydrochloride is also yellow and melts at 179-180 C.

5.5 grams of 2-(,B-diethylamino-ethylamino)-3:S-dinitro-pyridine are dissolved in 50 ml. of alcohol at 70 C., 11 ml. of concentrated ammonia solution are added, and the solution is saturated with hydrogen sulfide gas at that temperature. The solution is then evaporated in vacuo, the residue is taken upin 10 ml. of 5 N-hydr'ochloric acid, the solution is treated with animal charcoal and then filtered, and the filtrate is rendered alkaline with ammonia. The base is taken up in ether, the ethereal solution is dried with magnesium sulfate, the solvent is removed, and the base is purified by way of its hydrochloride. The base is liberated from its hydrochloride in' aqueous solution by means of ammonia and is crystallized from benzene.

The 2- B-diethylamino-ethylamino -3-amino-5-nitropyridine of the formula IlCH2CH:N( r s)z has a brown-red color and melts at 83 C. Its hydrochloride melts at ZOO-205 C.

Example 2 Its hydrochloride melts at 258 C. r

The base used as starting material, namely 2-(Bdimethylamino-ethylamino)-3-amino-5-nitropyridine, is pre pared as follows:

To 44.4 grams of 2-chloro-3':S-dinitropyridine, dissolved in 300 ml. of toluene, are added dropwise, while stirring, at C. 38 grams of dimethylamino-ethylamine dissolved in ml. of toluene. When the addition is complete the reaction mixture is boiled under reflux for 2 hours, then cooled to room temperature, and stirred with 100 ml. of a 2 N-solution of caustic coda. The toluene layer is removed, washed with water and thoroughly agitated with 300 ml. of 2 N-hydrochloric acid. The yellow crystalline hydrochloride is filtered off and washed with a small amount of benzene. The resulting '2 (,8 dirriethyl amino ethylamino) 3:5 dinitropyridine hydrochloride melts at 268270 C.

To 29.5 grams of the latter hydrochloride dissolved in 300ml. of ethanol, which contains 60 ml, of a concentrated aqueous solution of ammonia, there are sidissolved in 100 ml. of water and 32 grams of ammonium chloride also dissclved in 100 ml. of water in the course of 1 hour. The temperature rises to 40 C. during the dropwise addition. When the addition is complete the whole is stirred at room temperature for 3 hours, then adjusted to a pH value of 3-4 with hydrochloric acid (1:1), whereupon the hydrochloride crystallises out. The latter is dissolved in the minimum quantity of Water, the solution is clarified with animal charcoal, and, after rendering the solution alkaline with ammonia, the red crystalline 2-(fl-dimethylamino-ethylamino)-3-amino-5-nitropyridine'melting at 137-138 C. is obtained.

Example 3 I, A mixture of 7.6 grams of 2(/8-diethylamino-ethylamino)-3-amino-5-nitro-pyridine and 9 grams of urea is heall fi at o- 0 C. until the splitting off of ammonia substantially ceased -(4- hours). The meltis dissolved inllll) ml. ofa'lcohol, the solution is clarified with animal charcoaland rendered weakly acid with alcoholic hydrochloric acid, whereupon the hydrochloride of 1- (B diethylamino ethyl) 2 hydroxy-5-nitro-7-azabenzimidazole of the formula 411 kW i .OH2CHiN.(C2Hr)1 melting at 240 C. crystallises out.

Example 4 1--- (5 dimethylamino-ethyl) -:2 hydroxy :5 nitro-7-azabenzimidazole of the formula OzN N is obtained in :a manner analogous to'that described in Example 3 by heating 2-(5-dimethylamino-ethylamino)- .3 amino 5-nitropyridine with urea. Its hydrochloride melts at 203-205 C.

Example 5 A solution of 8.4 grams of 3-amind4-(B-diethylaminoethylamino)-pyridine in 50 ml. of glacial acetic acid is boiled under reflux for 16 hours. The solution is then evaporated in 'vacuo, -a 2 TN-solution of caustic soda is added to the residue, and the alkaline aqueous solution is extracted with chloroform. The chloroform extracts are washed with water, dried over magnesium .sulfate filtered and evaporated.

The residue is distilled in a high vacuum, whereby 1- (fi diethylamino ethyl) -2 methyl 5 azabenzimidaz'ole of the formula passes over as a colorless oil boiling at 170-172" C. under 0.04 Tor.

By adding to a solutionof the base in a small amount of methanol the calculated quantity of hydrochloric acid in ethyl acetate there is obtained in the dihydrochloride which melts at 260-262 after recrystallization from a mixture of methanol and ether.

The 3 amino- 4 (B diethylamino ---ethylamino') pyridine used as starting material is prepared as follows:

To a solution of 13.5 grams of diethylamino-ethylamine in 7 0 :ml. of absolute toluene at room temperature isadded dropwise, while stirring, a solution of 12.3 grams of s3-nitro4-chloropyridine:in 20 ml. of absolute toluene. Whenthe mixture has been stirred for 2 hours at 80 0., the cooled reaction mixture is extracted with dilute hydrochloric acid, the acid solution is rendered alkaline with an aqueous solution'of ammonia'and extracted'with chloroform.

The residue obtained by evaporating "the chloroform is distilled in a highvacuum, whereby 3-nitro-4-(18-diethyl-amino-ethylamino)-pyridine is obtained as a red oil boiling at l41-l43-C. under:0.05 Tor.

12.5 grams of the latter nitro-compound are dissolved in 70 ml. of alcohol and hydrogenated in the presence of a nickel or palladium catalyst until the theoretical quantity of hydrogen has been absorbed. The mixture is filteredto remove the catalyst, the solution-is evaporated under reduced pressure, and the residue is distilled a vacuum, whereby 3-.amino-4-(fl-diethylamino-ethy1- 6 amino)- pyridine .is obtained as a viscous oil boiling at 155-160 'C. under0.07 mm. pressureof mercury. 'Its dihydrochloride melts at 244-247 with decomposition.

Example 6 Usingthe process described in Example 5 and formic acid Of'98% strength instead of glacial acetic acid, there "is "obtained 1- (,B-diethylamino-ethyl) -5-aza-benzimidazole of the formula Q 1 V I GH2UH2- N(Cr Hs)2 in the form of a-colorless oil boiling at C. under 0.03 mm. of pressure whose dihydrochloride melts at -'225-226 C.

When propionic acid is used instead of glacial acetic acid, there is obtained l-(fi-diethylamino-ethyl)-2-ethy1- 5-azabenzimidazole of the formula \CC2H5 Hg-C'H2' N (C 235) in the form of a-colorless oil boiling at -150" 'C.'under 0.02 mm. of pressure.

When isobutyric acid is used and the reaction mixture is boiled for at least 48 hours there is obtained l-(B-di- 'etliylamino ethyl) 2 -'isopropyl 5 azabenzimidazole of the formula C-'=CH(CHa): CH2VG Hz-N C2H5) 2 in the form of a colorless oil boiling-at -155 under 0.02 mm. of pressure.

Example 7 '9 grams of carbon disulfide are added to a solution of '12 grams of *3-amino-4-(fl-diethylamino-ethylamino)- pyridine in 60 cc. of absolute methanol and the whole boiled gently under reflux for 16 hours. The reaction solution is evaporated on a water bath under reduced pressure, and the solid residue recrystallized from a'mixture of ethanol and petroleum ether, l-(p-diethylamin'oethyl)-2-mercapto-5-azabenzimidazole of the formula iHs-CH2N(C2E5)2 being obtained in the form of faintly yellow crystals melting at l75-176 (3., whose hydrochloride melts at 248-250? C. with decomposition.

Example 8 C- 44 grams of this nitro compound are dissolved in 200 {passing over as acolorless oil boiling at 135-140 C. under 0.05 mm. of pressure. The dihydrochloride melts at '240-242 C.

The 3 amino 4 ([3 -,dimethylamino-ethyl-amino)- pyridine used as starting material is prepared as follows:

A solution of 46 grams of 3-nitro-4-chloropyridine in :50 cc. of absolute toluene is added dropwiseto a solution of 38.2 grams of dimethylamino-ethylaminein 200 cc. of

absolute tolueneat room temperature with stirring. The t mixture is stirred for 2 hours at 80 C., the cooled reaction mixture extracted with dilute hydrochloric acid, the acidic solution rendered alkaline with aqueous ammonia solution and extracted with chloroform.

The solid yellow chloroform residue is recrystallized 'from a mixture of ethyl acetate and petroleum ether, 3- nitro-4-(fi-dimethylamino-etl1ylarnino)pyridine being obtained in the form of yellow crystals melting at 97-985 Hr-CHQN(CH3)2 injthe form of a faintly yellow oil boiling at 135-140 C. under 0.06 mm. of pressure, whose dihydrochloride melts at 288-289 C. with decomposition.

Example 9 A solution of 14.5 grams of 3-amino-4-( 8-morpholinoethylamino)-pyridine in 100 cc. of formic acid of 98% strength is boiled under reflux for 16 hours, evaporated under reduced pressure, the residue treated with concentrated ammonia solution and extracted with chloroform.

The solid chloroformic residue is recrystallized from a mixture of ethyl acetate and petroleum ether, l-(flmorpholino-ethyl)--azabenzimidazole of the formula being obtained in the form of colorless crystals melting at 106-108" 0., whose dihydro-chloride melts at 269- 271 C. with decomposition.

f 'The 3 amino 4 (e morpholino ethylamino)- pyridine used as starting material can be prepared as follows:

. By reacting 52.5 grams of morpholino-ethylamine with 43 grams of 3-nitro-4-chloro-pyridine bythe process described for 3-nitro-4-(fi-diethylamino-ethylamine)-pyridine in Example 5, there is obtained 3-nitro-4-(B-morpholino-ethylamino)-pyridine as a viscous brown oil boiling at 190-194 C. under 0.08 mm. of pressure.

By hydrogenation of the nitro compound in alcoholic solution with a nickel or palladium catalyst until the theoretical quantity of hydrogen has been taken up, 3- amino-4-(fl-morpholino-ethylamino)pyridine is obtained as a faintly brown oil boiling at 190-195 C. under 0.08 mm. of pressure. i

' If the baseis boiled with glacial acetic acid instead of formic acid, l-(fi-morpholino-ethyl)-2-methyl-5-aza benzimidazole of the formula KL I - (Jar-omis obtained as a faintly yellow oil boiling at 185-190 C. under 0.07 mm. of pressure whose dihydrochloride melts at 281-282 C. with decomposition.

* 1 .03 die thylaminof ethyl) 2 7-azabenzidimida2ole'ofthe formula N illiz-ClIr-N'(CzHtOa prepare d from 2-(fi-diethylamino-ethylamino) -3 amino 5-nitropyridine and propionic acid at ll0-120 C. by the process described in Example 1, melts at'65-66 C.; its hydro-chloride melts at 215-216 C.

l (B diethylamino ethyl) 2 propyl 5 7-azabenzimidazole of the formula ethyl 5 nitro- OaN - nitro- OzN N I CH,CHa-CH; CHr-CHz-N(CzHs)2 prepared in the same manner from butyric acid, melts at 72-73 C.; its hydrochloride melts at 184-185 C.

Example 11 OzN Example I 2 14.75 grams of l-(fl-diethylamino-ethyl)-2-mercapto- -5-nitro-benzimidazole are, added to a sodium methylate solution prepared from 1.25 grams of sodium and 200 cc. of mehanol, and 3.5 cc. of methyl iodide are then added dropwise. After being allowed tostand overnight under reduced pressure, the reaction mixture is taken up in water and ether, the ethereal solution washed with sodium carbonate solution and water, dried over magnesium sulfate and evaporated. The remaining l-(B- diethylamino ethyl) 2 methylmercapto 5 nitro- 7-azabenzimidazole of the formula f sh...

OzN

V V CPn-om-Nwm), melts at 86-87" C. after crystallization from alcohol; its hydrochloride melts at 206207 C.

Example 13 5 11 grams of propionic acid nitrile are saturated in cc. of chloroform and 11.5 cc. of absolute alcohol at 0 C. with h dro en cb.loride,'allowed to stand overnight and evaporated under reduced pressure at a temperature of 30 C. at the most. The remainingimino ether -hydrochloride is stirred with 6.8 gramsof Z-(dimethylaminoethylamino)-3-amino-5-nitro-pyridine in 80 cc. of propionic acid at 50C., the reaction mixture evaporated under reduced pressure, the residue 'taken up in aqueous hydrochloric acid and extracted withether. The acidic aqueous solution is then rendered alkaline "withaqueous ammonia, extracted with chloroform, the chloroformic extract agitated with sodium carbonate solution and dried over magnesium sulfate and evaporated. The remaining 1 (B dimethylamino ethyl) 2 ethyl nitro 7- azabenzimidazole of the formula OzNfTN I CHr-CHPN(CH3)I melts at 98-100'C. after crystallizationirorn ether; its hydrochloride melts at 237-238" .C.

Example 14 distills in a bulb tube at 125 C. under 0.07 mm. of

pressure.

The 2 (,8 diethylamino ethylamino) 3 nitropyridine used as starting'material is obtained as follows:

.23 grams of 2-chloro- 3-nitro pyridineare dissolved in 150 cc. of toluene with heating and added dropwise at 80C. to :26 .cc. of 'B-diethylamino-iehtylamine in 50 cc. of toluene. The whole is then boiled for two lhours, cooled, sodium hydroxide solution is added until theiimix- :ture shows an alkaline reactionga'nd the toluenesolution extracted with hydrochloric acid. The acidic aqueous solution is rendered alkaline "with aqueous ammonia, extracted with ether and the extract washed with sodium chloride, dried over magnesium sulfate andevaporated. The remaining 2-(fi-diethylamino-ethylamino') e3'-=nitro pyridine distills in a bulb tube at 120 C. under 0.05 mm. of pressure.

Example 15 2 (B dimethylamino ethylamino) 3 amino pyridine, obtained by hydrogenating 21.1 grams of 2-(fi-dimethylamino-ethylamino)-3-nitro-pyridine in 200 cc. of ethanol in the presence of 5 grams of Raney nickel and by evaporation, is boiled for 2 hours in 70 cc. of formic acid. The reaction mixture is evaporated under reduced pressure, the residue taken up in water, rendered alkaline with ammonia solution, extracted with ethyl acetate, dried and evaporated. The remaining l-(B-dimethylaminoethyl)-7-azabenzimidazole of the formula distills in a bulb tube at 115 C. under 0.05 mm. of pressure.

:10 The .2-(fi-dimethylamino-ethylamino)smite-pyridine used as starting material can be prepared in .a manner analogous to that described in Example 14 forZ-(fi-diethylamino-ethylamino)-3-nitro-pyridine and .melts .at 58-59 C. after crystallization from ether.

Example '16 9 grams of 3-amino-4-(p-dimethylamino-ethylamino)- S-nitro-pyridine are boiled under reflux for 3 hours in 30 cc. of formic acid. The mixture is then evaporated under reduced pressure, theresidue taken up in water, rendered alkaline with ammonia and extracted'with ether. The ethereal extract is dried over magnesium sulfate and evaporated to yield 1-(B-dimethylamino-ethyl)-7-nitro-5- azabenzimidazole of the formula OHr- C'HrN (CH3):

from a mixture of ether and hexane. Melting point: 76-78 C.; its hydrochloride melts at 252 C.

The 3-amino-4-(fi-dirnethylamino-ethylamino)-5-nitropyridine used as starting material can be prepared as follows:

20 grams of 4-chloro-3:5 dinitro-pyridine dissolved in 120 cc. of toluene are added dropwise to 19.5 grams of dimethylamino-ethylamine and 300 cc. of toluene at 80 "C., and stirred for one-hour at 80 C. The reaction mixture is then cooled, aqueous ammoniais added until the mixture gives an alkaline reaction, and the toluene solution extracted with hydrochloric acid. The acidic aqueous solution is then again rendered alkaline with ammonia and precipitating crystalline 4-( 3-dimethyl- -amino-ethylamino)-3 :S-dinitro-pyridine filtered ofi. v

16 grams of 4-(fi-dimethylamino-ethylarriino)-3z'S-dinitro-pyridine are converted into the hydrochloride, dissolved in 190 cc. of alcohol and 37.2 cc. of concentrated ammonia, and 20.8 grams'of sodium hydrogen sulfide of 73% strength in 60 cc. of water and 21 grams of ammonium chloride in 60 cc. of water are added dropwise simultaneously. The whole is then stirred for three hours, hydrochloric acid is added until the mixture gives an acid reaction, the precipitated sulfur is filtered oil and the filtrate concentrated'to cc. The filtrate is rendered alkaline with concentrated ammonia and extracted with benzene. The benzene extract is dried with magnesium sulfate and evaporated to yield 3-amino-4-(B-dimethylamino-ethylamino)-5-nitro-pyridine from a mixture of benzene and hexane. The product melts at 98-100 C.

Example 17 0.95 g. of 5(6)-nitro-7(4)-azabenz-imidazole are suspended in 50 ml. of ethanol and mixed with a-solution of 0.15 g. of sodium in 30 mlrof ethanol, the nitro compound, as orange-colored salt, passing into solution. In the course of 10 minutes there is added dropwise, while stirring, a solution of 0.8 g. of B-diethylamino-ethylchloride in 20 ml. of ethanol, the color of the reaction solution turning from orange to yellow. When the addition is complete, the mixture is stirred for 1 hour at 60 C. and then evaporated under reduced pressur The residue is agitated with a mixture of 10 ml. of 2 N-sodium hydroxide solution and 100 ml. of ether, the ethereal extract is washed twice with saturated sodium chloride solution, dried over magnesium sulfate, and evaporated. The residual oil is mixed with one equivalent of alcoholic hydrochloric acid and the hydrochloride crystallized by the careful addition of ether. The hydrochloride so obtained melts unsharply at -180 C. and consists of two isomers which can be separated to a large extent by fractional crystallization from alcohol. From the hydrochlorides thus purified there can be isolated by liberating the bases and recrystallizing the latter from a mixture of ether and pentane, the l-(fi-diethylamino-ethyl)-5-nitro-7-azabenzimidazole of melting point 6667 C. (melting point of the hydrochloride 206-208. C.), of the formula and the isomeric -1-(fl-diethylamino-ethyl)-6-nitro-4-azazbenzimidazole or the formula a can be prepared by the following series of reactions:

11 g. of iZ-chloro-3,5-dinitropyridine are dissolved in 80 ml. of alcohol and admixed dropwise, while stirring, with a mixture of 30ml. of concentrated ammonia solu, tion and 80 m1. of alcohol. During the addition, the

' solution turns orange-yellow, and an orange-yellow product crystallizes soon; When the addition is complete, stirring is continued for 15 minutes, the reaction mass then cooled to C., and filtered. The resulting Z-amino- 3,5-dinitropyridine melts at l90192 C.

8.8 got this compound are mixed with a mixture of 94 ml. of alcohol and 27 ml. of concentrated ammonia solution, and to the suspension are simultaneously added dropwise, while stirring,,in the course of 15 minutes a solution of 16.2 g. of sodium hydrosulfide in 47 ml. of water and .a solution 0516 g. of ammonium chloride in '47 ml. of water. The reaction mixture assumes a deep red coloration, and a dark red product soon crystallizes out. After three hours, the product is filtered off with suction and washed with a lz'l-mixture of alcohol and ether. The 2,3-diarnino-5-1iitropyridine so obtained melts at 260 C.

5 g. of this nitrodiamine are heated under reflux for 20 minutes with ml. of formic acid, the mixture then evaporated under reduced pressure, and the residue 'triturated with water, given a pH of 6 with ammonia, and filtered with suction. This crude product is boiled with 200 ml. of alcohol in the presence of a small quantity of Norit, the solution filtered, and the orange-yellow filtrate concentrated to ml. to obtain a crystalline orangeyellow product, namely 5(6)-nitro-7(4)-azabenz-imidazole which gradually sinters and decomposes when heated above 260 C.;

' What is claimed is: 1. A member selected from the group consisting of a l-lower tertiary amino lower alkyl-azabenz-imidazole of the formula 7 7 xj I o-n.

I W. .A.

and non-toxic acid addition salts thereof in which A stands for-lower alkylene, and R for a tertiary amino substituent selected from the group consisting of di-lower alkylarnino, pyrrolidino, piperidino, morpholino and piperazinc, and in which R stands for a member selected from 'the group consisting of hydrogen, hydroxy, merca'pto,

lower alkyl, lower alkoxy, lower alkylmerc'apto and halogen and X stands for the bonds necessary to complete a G-mernbered pyridine ring selected from the group consisting of the unsubstituted pyridine ring and the monosubstituted pyridine ring the substituents on said pyridine ring being selected from the group consisting of hydroxy,

mercapto, lower alkyl, lower alkoxy, lower alkylmercapto halogen and nitron 2. An azabenzimidazole ofthe formula of the compounds No references cited. 

1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF A 1-LOWER TERTIARY AMINO LOWER ALKYL-AZABENZ-IMIDAZOLE OF THE FORMULA 